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Trichoblastomas are benign cutaneous adnexal tumours which originate in the hair follicle germs. They are considered to be extremely rare and usually present in the head and neck region. Clinically, they present as flesh-coloured nodular growths mimicking the more commonly found basal cell carcinoma (Stanoszek et al., 2017 Nov) [ 1 ]. These tumours can potentially undergo malignant transformation which again is extremely infrequent.

Aims: Orthognathic surgery corrects craniofacial and dentofacial disproportion that compromises breathing, masticatory function, and aesthetics. A patient's typology influences their psychosocial and physical pre-operative expectations and post-operative perceptions and is an emerging area of research. This study aims to evaluate subjective expectations and/or perceived outcomes of orthognathic surgery; and whether orthognathic surgery meets patient expectations. Method: A questionnaire-based cross-sectional survey was administered pre- and post-operatively. Typologically, patients were classified as metamorphosisers – those with high expectation of psychosocial and physical transformation; evolvers – opposite of metamorphosisers; pragmatists – those with low expectation of psychosocial and high expectation of physical transformation; or shedders – the opposite of pragmatists. A Chi-Square goodness fit test with p

There is no doubt that one of the major advances in fracture management has been the development of direct osteosynthesis techniques, enabling precise fixation of the bones. This allows for earlier return to function and improved aesthetics and avoids external frames and wires. Stepwise improvements in plate profile and implant design have greatly facilitated and improved surgical outcomes. Titanium plates have now been used routinely for osteosynthesis in maxillofacial trauma for over 30 years, reflecting their reliability, predictability and biocompatibility.

Integrins are widely expressed plasma membrane adhesion molecules that tether cells to matrix proteins and to one another in cell-cell interactions. Integrins also transmit outside-in signals that regulate functional responses of cells, and are known to influence gene expression by regulating transcription. In previous studies we found that platelets, which are naturally occurring anucleate cytoplasts, translate preformed mRNA transcripts when they are activated by outside-in signals. Using strategies that interrupt engagement of integrin alphaIIbbeta3 by fibrinogen and platelets deficient in this integrin, we found that alphaIIbbeta3 regulates the synthesis of B cell lymphoma 3 (Bcl-3) when platelet aggregation is induced by thrombin. We also found that synthesis of Bcl-3, which occurs via a specialized translation control pathway regulated by mammalian target of rapamycin (mTOR), is induced when platelets adhere to immobilized fibrinogen in the absence of thrombin and when integrin alphaIIbbeta3 is engaged by a conformation-altering antibody against integrin alphaIIbbeta3. Thus, outside-in signals delivered by integrin alphaIIbbeta3 are required for translation of Bcl-3 in thrombin-stimulated aggregated platelets and are sufficient to induce translation of this marker protein in the absence of thrombin. Engagement of integrin alpha2beta1 by collagen also triggered synthesis of Bcl-3. Thus, control of translation may be a general mechanism by which surface adhesion molecules regulate gene expression.

Circulating human platelets lack nuclei, cannot synthesize mRNA, and are considered incapable of regulated protein synthesis. We found that thrombin-activated, but not resting, platelets synthesize Bcl-3, a member of the IκB-α family of regulatory proteins. The time- and concentration-dependent generation of Bcl-3 in platelets signaled by thrombin was blocked by translational inhibitors, by rapamycin, and by inhibitors of phosphatidylinositol-3-kinase, indicating that it occurs via a specialized translational control pathway that involves phosphorylation of the inhibitory protein 4E-BP1. After its synthesis in activated platelets Bcl-3 binds to the SH3 domain of Fyn (p59 fyn ), a Src-related tyrosine kinase. This, along with its expression in anucleate cells, suggests that Bcl-3 has previously unrecognized functions aside from modulation of transcription. We also demonstrate that platelets synthesize and secrete numerous proteins besides Bcl-3 after they adhere to fibrinogen, which mediates adhesion and outside–in signaling of these cells by engagement of αIIb/β3 integrin. Taken together, these data demonstrate that regulated synthesis of proteins is a signal-dependent activation response of human platelets.

Nitric oxide (NO) is an endogenous protectant against reperfusion-induced ventricular fibrillation (VF) in the rat isolated heart. Here, the following were investigated: (1) the tissue source of cardioprotective NO using a novel inhibitor (7-nitro indazole; 7-NI) of the neuronal form of NO synthase (NOS) and direct detection of coronary effluent NO by chemiluminescence; and (2) the species dependence by comparing rat and rabbit hearts. Perfusion with modified Krebs solution was followed by 60 min left regional ischemia and 10 min reperfusion. 7-NI (1 microM) increased the incidence of VF from 0% to 60% in rat hearts (n = 10; P0.05). Co-perfusion with L-arginine (1 mM) reduced VF incidence to 20% (P:N.S. v controls). The inactive analog of 7-NI (6-amino indazole: 6-AI) had no pro-fibrillatory activity. Neither 7-NI nor 6-AI affected coronary flow or recovery of flow during reperfusion. 7-NI reduced basal coronary effluent NO levels to below the limit of detection (1 pmol), but a massive increase in NO levels occurred when L-arginine was co-perfused with 7-NI. Although 7-NI had no effect on basal coronary flow and, by implication, resting NO release, it was found, in separate studies, to antagonise substance P-induced vasodilatation and NO release, suggesting that its neuronal selectivity is lost in the presence of an exogenously administered activator of endothelial NOS in rat hearts. In rabbit hearts, in contrast, 7-NI had no effect on VF or NO levels. However, in rabbit hearts the isozyme non-selective NO synthase blocker, NG-nitro-L-arginine methyl ester (L-NAME; 100 microM), increased VF incidence from 0 to 50% (P0.05) and, during the first minute of reperfusion, reduced NO levels from 4929 +/- 893 to 2505 +/- 483 pmol/min/g (P0.05) and recovery of coronary flow by 22% (P0.05). Each of these effects were prevented by L-arginine co-perfusion. These data indicate a role for basally released NO as an endogenous antifibrillatory cardioprotectant in rat and rabbit isolated heart and indicate that the tissue source (neuronal in rat but not in rabbit heart) is species-dependent.

1. After a period of myocardial ischaemia, reperfusion of the myocardium can elicit cardiac arrhythmias. Susceptibility to these arrhythmias declines with time, such that a preceding period of more than approximately 40 min ischaemia is associated with few reperfusion-induced arrhythmias. We have tested the hypothesis that this decline in susceptibility occurs, in part, because of protection by endogenous guanosine 3':5'-cyclic monophosphate (cyclic GMP). 2. Rat isolated hearts were subjected to 60 min left regional ischaemia followed by reperfusion (n = 10 per group). Methylene blue (20 microM), a soluble guanylate cyclase inhibitor, raised the incidence of reperfusion-induced ventricular fibrillation (VF) from 10% in control hearts to 80% (P < 0.05). This effect of methylene blue was abolished by co-perfusion with zaprinast (100 microM), a phosphodiesterase inhibitor which, in the rat heart, is cyclic GMP-specific (specific for the type-V phosphodiesterase isozyme). 3. Methylene blue reduced cyclic GMP levels in the ischaemic, non-ischaemic and reperfused myocardium (P < 0.05) to 50 +/- 10, 52 +/- 12 and 70 +/- 7 fmol mg-1 tissue wet weight, respectively from control values of 143 +/- 38, 147 +/- 43 and 156 +/- 15 fmol mg-1. Co-perfusion with zaprinast prevented this effect, and cyclic GMP levels were actually elevated (P < 0.05) to 366 +/- 102, 396 +/- 130 and 293 +/- 22 fmol mg-1 in ischaemic, non-ischaemic and reperfused myocardium, respectively. Zaprinast by itself also elevated cyclic GMP content. Cyclic AMP levels were not affected by zaprinast or methylene blue. 4. In conclusion, when endogenous cardiac cyclic GMP synthesis is reduced, susceptibility to reperfusion-induced VF after sustained ischaemia is substantially increased. The effect is prevented by inhibiting cyclic GMP degradation. Therefore cyclic GMP appears to be an endogenous intracellular cardioprotectant, and its actions may account for the low susceptibility to VF normally encountered in hearts reperfused after sustained ischaemia.

Abstract It has been proposed that NO may function as an endogenous cardioprotectant. We have investigated whether modulation of NO levels (detected in coronary effluent by chemiluminescence) by a blocker of its synthesis, by supplementation of its precursor, and by administration of an NO donor can influence reperfusion arrhythmias in the isolated rat heart. Rat hearts were perfused with modified Krebs’ solution and subjected to 5, 35, or 60 minutes of left regional ischemia followed by 10 minutes of reperfusion. N G -Nitro- l -arginine methyl ester (L-NAME), which blocks NO synthase, increased the incidence of reperfusion-induced ventricular fibrillation (VF) from 5% in the control condition to 35% after 60 minutes of ischemia (n=20, P l -arginine (an NO precursor) but persisted in hearts coperfused with d -arginine (1 mmol/L). L-NAME did not increase VF susceptibility in hearts reperfused after 5 or 35 minutes of ischemia. L-NAME caused sinus bradycardia (264±10 versus 309±5 bpm in control groups, P −1 · g −1 tissue in controls, P −1 · g −1 ( P l -arginine (10 344±1730 pmol · min −1 · g −1 , P P =NS). The NO donor sodium nitroprusside (10 μmol/L) significantly increased coronary flow 1 minute before ischemia (15.4±1.1 versus 9.2±0.6 mL · min −1 · g −1 tissue and coronary effluent NO levels (from 1122±122 to 4093±1466 pmol · min −1 · g −1 , P

In the present study a novel nitric oxide (NO) donor, CAS-1609, was utilized as a means of coronary NO replenishment in a canine model of myocardial ischemia-reperfusion. Administration of CAS-1609 (1.25 mg iv) 10 min before reperfusion, followed by a 1 mg/h intracoronary infusion throughout the 4.5-h reperfusion period, resulted in significant improvement in postischemic transmural myocardial blood flow (0.66 +/- 0.09 vs. 0.37 +/- 0.08 ml.min-1.g-1 for saline vehicle, P < 0.05). Dogs receiving NO supplementation also exhibited a significant recovery of myocardial contractility after 4.5 h of reperfusion (30 +/- 2% area ejection fraction vs. 22 +/- 2% for saline vehicle, P < 0.05). Moreover, myocardial necrosis as a percentage of the area at risk was reduced from 28.9 +/- 4.3% in the saline group to 8.5 +/- 2.6% in the CAS-1609 group (P < 0.01), while ischemic zone myeloperoxidase activity, indicative of neutrophil infiltration, was also attenuated by 70% with NO therapy. Injection of acetylcholine and nitroglycerin into the left circumflex coronary artery revealed a significant impairment of vasodilator responses in the saline vehicle dogs at 2 h of reperfusion. However, dogs treated with the NO donor demonstrated postischemic vasodilator responses which were similar to baseline (P = not significant vs. baseline). These studies demonstrate that intracoronary administration of NO significantly augments postischemic coronary blood flow and contractile function following ischemia and reperfusion. In addition, NO therapy reduces coronary vascular injury, attenuates myocardial necrosis, and reduces neutrophil infiltration. The cardioprotective actions of intracoronary NO administration may be related to the potent antineutrophil actions of NO.

The refashioning of the many distinct structures necessary for successful anatomical and aesthetic reconstruction of the nose after total rhinectomy is difficult. Several significant operations are needed to produce good aesthetic results with functional patency of the nasal airway. We describe a method using autologous grafts that has produced good results on both occasions when it was done. It has the advantage of only one major operation and one subsequent minor revision.

Subacute haematogenous osteomyelitis of the talus in children is a rare condition. All previously reported cases have been managed by hospital admission with surgical debridement and antibiotics or by intravenous antibiotic therapy followed by oral antibiotics. This case series documents the management of the condition at our institution and reviews the current published literature. We conclude that with appropriate patient selection, primary subacute haematogenous osteomyelitis of the paediatric talus can be managed on an out-patient basis with oral antibiotic therapy.

Nitric oxide (NO) released from endothelium mediates the vasodilatation caused by numerous autacoids. Nitric oxide can also be exogenous in that some drugs used in cardiovascular disease are NO donors (e.g. glyceryl trinitrate, sodium nitroprusside and isosorbide mononitrate used in angina). However, the notion that NO is a cardiac protectant, whose mimicry or supplementation is desirable, has recently been questioned by data that suggest it is an innocent bystander in some conditions, and even a pathological mediator of dysfunction in others. This important issue is discussed by Mike Curtis and Ravinder Pabla who suggest it is necessary to reappraise the role of NO modulation in cardiac pharmacotherapy.

Nitric oxide (NO) protects the heart against some forms of reperfusion-associated dysfunction (e.g. arrhythmias). Its role in protecting against other types of dysfunction is controversial. NO ameliorates polymorphonuclear cell-induced exacerbation of stunning. Here, whether endogenous NO protects against contractile dysfunction in a polymorphonuclear cell-free model has been tested. Isolated rat hearts (n = 6 per group) were perfused with Krebs solution for 15 min. They were then perfused with test solution: Krebs, or Krebs containing 100 microM NG-nitro-L-arginine methyl ester (L-NAME) (a concentration shown previously to significantly reduce NO content in coronary effluent), 100 microM L-NAME plus 10 mM L-arginine (the latter shown previously to be sufficient to surmount the effect of L-NAME), or 10 mM L-arginine alone. After 10 min of this, the hearts were subjected to 60-min normothermic global ischemia followed by reperfusion with the same test solution as before. A time-matched (sham) group was perfused continuously with Krebs. L-NAME hastened the onset of ischemic contracture (P < 0.05) and increased its peak value from 67.8 +/- 4.6 mmHg to 93.0 +/- 4.9 mmHg (P < 0.05). Both effects were prevented by co-perfusion with 10 mM L-arginine. Initially, reperfusion exacerbated diastolic contracture, but diastolic pressure at a constant ventricular volume fell from 112 +/- 27 mmHg to 73 +/- 19 mmHg between the 5th and 60th min of reperfusion in drug-free hearts, indicative of recovery from diastolic stunning. This recovery was not exacerbated or lessened by perfusion with L-NAME or L-arginine. Left ventricular developed pressure increased from 42 +/- 2 mmHg to 106 +/- 18 mmHg in controls between 5 and 30 min after the start of reperfusion, the latter value being indistinguishable from that in the sham group. At this time, the value in the L-NAME group was similar (78 +/- 18 mmHg). This indicated complete recovery from systolic stunning in both groups 30 min after the start of reperfusion. However, earlier after the start of reperfusion, there had been zero pressure development in the L-NAME group (P < 0.05 v the control group). This was associated with severe impairment of recovery of coronary flow, e.g. of only 18% of the mean coronary flow in controls 5 min after the start of reperfusion (P < 0.05). At 30 min after the start of reperfusion (when systolic function had recovered in the L-NAME group), flow recovery had increased in this group to 96% of the mean control values. The impairment in rates of recovery of systolic function and coronary flow in the L-NAME group were each prevented by coperfusion with L-arginine (P < 0.05). In conclusion, endogenous NO may delay the onset and reduce the magnitude of ischemic contracture but despite this, appears not to facilitate early recovery from systolic and diastolic stunning as a result of any direct action in the myocardium. The beneficial effect it does possess in this polymorphonuclear cell-free preparation is transient and results from mediation of rapid recovery of coronary flow during reperfusion.

Abstract With the knowledge of NO as an antiadhesion molecule, we performed studies to investigate the effects of NO on postischemic polymorphonuclear leukocyte (PMN)–mediated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minutes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 million) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline values. Infusion of PMNs alone (n=10) led to a 61% reduction in left ventricular developed pressure (LVDP) and a 57% reduction in the pressure-rate product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor, CAS-754 (n=9), resulted in 80.2±6.7% recovery of LVDP and 77.0±8.6% recovery of PRP. Treatment with l -arginine (2.5 mmol/L, n=10) resulted in a similar improvement in the postischemic contractile state of the heart. In contrast, N G -nitro- l -arginine methyl ester (L-NAME) treatment (250 μmol/L, n=10) resulted in an exacerbation of contractile dysfunction, as evidenced by a 93% reduction in LVDP at 45 minutes of reperfusion and a 91% reduction in PRP. The deleterious effects of L-NAME were prevented by l -arginine coperfusion. We failed to observe any cardioprotective effects when NO or l -arginine was administered to hearts subjected to 25 minutes of ischemia and 45 minutes of reperfusion in the absence of PMNs. In conclusion, PMN-mediated myocardial contractile dysfunction is attenuated by NO and exacerbated by blockade of NO synthesis.